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基于可重复使用电化学传感器的可靠临床血清分析:迈向抗精神病药物氯氮平的即时检测

Reliable clinical serum analysis with reusable electrochemical sensor: Toward point-of-care measurement of the antipsychotic medication clozapine.

作者信息

Kang Mijeong, Kim Eunkyoung, Winkler Thomas E, Banis George, Liu Yi, Kitchen Christopher A, Kelly Deanna L, Ghodssi Reza, Payne Gregory F

机构信息

Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD 20742, United States; Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, United States.

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, United States; MEMS Sensors and Actuators Laboratory (MSAL), University of Maryland, College Park, MD 20742, United States.

出版信息

Biosens Bioelectron. 2017 Sep 15;95:55-59. doi: 10.1016/j.bios.2017.04.008. Epub 2017 Apr 12.

Abstract

Clozapine is one of the most promising medications for managing schizophrenia but it is under-utilized because of the challenges of maintaining serum levels in a safe therapeutic range (1-3μM). Timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine, which is however challenging due to the complexity of serum samples. We demonstrate a robust and reusable electrochemical sensor with graphene-chitosan composite for rapidly measuring serum levels of clozapine. Our electrochemical measurements in clinical serum from clozapine-treated and clozapine-untreated schizophrenia groups are well correlated to centralized laboratory analysis for the readily detected uric acid and for the clozapine which is present at 100-fold lower concentration. The benefits of our electrochemical measurement approach for serum clozapine monitoring are: (i) rapid measurement (≈20min) without serum pretreatment; (ii) appropriate selectivity and sensitivity (limit of detection 0.7μM); (iii) reusability of an electrode over several weeks; and (iv) rapid reliability testing to detect common error-causing problems. This simple and rapid electrochemical approach for serum clozapine measurements should provide clinicians with the timely point-of-care information required to adjust dosages and personalize the management of schizophrenia.

摘要

氯氮平是治疗精神分裂症最有前景的药物之一,但由于将血清水平维持在安全治疗范围(1-3μM)存在挑战,其未得到充分利用。及时测定血清氯氮平水平已被确定为氯氮平更广泛应用的一个障碍,然而由于血清样本的复杂性,这具有挑战性。我们展示了一种用于快速测定血清氯氮平水平的基于石墨烯-壳聚糖复合材料的稳健且可重复使用的电化学传感器。我们在氯氮平治疗组和未治疗组精神分裂症患者的临床血清中的电化学测量结果,与集中实验室分析中针对易于检测的尿酸以及浓度低100倍的氯氮平的分析结果高度相关。我们用于血清氯氮平监测的电化学测量方法的优点包括:(i)无需血清预处理即可快速测量(约20分钟);(ii)具有适当的选择性和灵敏度(检测限为0.7μM);(iii)电极可在数周内重复使用;(iv)可进行快速可靠性测试以检测常见的导致误差的问题。这种用于血清氯氮平测量的简单快速的电化学方法应为临床医生提供调整剂量和个性化管理精神分裂症所需的即时护理点信息。

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